In the years since my laboratory at the NIDA IRP identified the sigma-1 receptor in 1982, many preclinical studies have shown that sigma-1 receptors and associated ligands are involved in stroke, amnesia, depression, cancer, Alzheimers disease, pain, and cocaine addiction. In this fiscal year, we have made a major discovery in the action of the sigma-1 receptor. We found that the sigma-1 receptor can interact with and change therefore the conformation of the dopamine transporter so that cocaine can be more efficiently block the dopamine uptake through the dopamine transporter. In addition, we found that the sigma-1 receptor agonist can potentiate the self-administration of cocaine. Thus, drugs that target the sigma-1 receptor may be of therapeutic value in treating cocaine addiction.